Protein-O-carboxylmethyltransferase (PCM) catalzes the transfer of a methyl group from S-adenosylmethionine to aspartyl residues on a variety of proteins. The function of this enzyme is not known, although it has been postulated to participate in the repair of defective proteins. It has also been suggested that it may participate in regulatory events for other enzymes. Previous work in our laboratory had shown that calmodulin binding proteins of a particularly good substrates for PCM and the activity of enzymes such as the calcium-dependent phosphodiesterase, calcineurin, and calmodulin-dependent protein kinase do indeed appear to be regulated by the methylation reaction. Using the expertise developed in this project, a new approach to the detection of binding proteins has been developed. In the specific case examined, calmodulin has been biotinylated, allowed to bind with appropriate proteins, and the bound calmodulin detected with an avidin linked peroxidase.